Targeting Inflammaging with Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF).

使用中脑星形胶质细胞衍生的神经营养因子 (MANF) 靶向炎症。

基本信息

批准号：
9247302
负责人：
Heinrich Jasper
金额：
$ 25.26万
依托单位：
BUCK INSTITUTE FOR RESEARCH ON AGING
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9247302
关键词：
Acute Age Age Factors Aging Aging-Related Process Anti-Inflammatory Agents Anti-inflammatory Astrocytes Biological Assay Cell Count Cell physiology Cells Chronic DNA Damage Data Disease Disease model Drosophila genus Epithelial Exhibits Functional disorder Genetic Genetic study Health Hemocytes Heterozygote Homeostasis Immune Infection Inflammation Inflammatory Inflammatory disease of the intestine Injection of therapeutic agent Injury Intervention Intestinal Intraepithelial Neoplasia Longevity Mediating Metabolic Modeling Mus Natural regeneration Outcome Study Phenotype Photoreceptors Proteins Retina Retinal Retinal Degeneration Retinal Diseases Role Serum Skin Stem cells Supplementation Testing Therapeutic Tissues Trachea Transgenic Organisms Translations Wild Type Mouse age related anti aging base fly inflammatory marker insight intestinal epithelium macrophage monocyte neurotrophic factor regenerative repaired research study tissue regeneration tissue repair tool

项目摘要

DESCRIPTION (provided by applicant): Low-level chronic inflammation is a hallmark of aging, and is a promising target for interventions that aim to delay the aging process. An important driver of systemic inflammation is the accumulation of pro-inflammatory (M1) macrophages. M1 Macrophages mediate acute inflammatory episodes after injury or infection, but to resolve inflammation, macrophages have to polarize into and anti-inflammatory (M2) phenotype. In preliminary studies, the applicants have identified Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) as an evolutionarily conserved modulator of immune cell polarization that promotes tissue repair in flies and mice. This function of MANF is required for tissue repair after damage, and can be harnessed to promote tissue regeneration in murine disease models. The applicants further found that serum MANF levels decrease with age, and that MANF deficiency in mice results in phenotypes that are consistent with widespread systemic inflammation. Based on these data, the applicants propose that MANF is a promising, evolutionarily conserved anti-geronic protein that can be used to delay or even reverse age-associated inflammatory phenotypes. To test this hypothesis, the applicants propose studies in flies and mice, pursuing three aims: (i) to characterize the effects of MANF on aging-related phenotypes in Drosophila, (ii) to assess the role of MANF in limiting age- related inflammation in mice, and (iii) to test MANF supplementation as a potential therapy for age-related diseases. The proposed studies will introduce MANF as an immune-modulatory anti-geronic protein that can limit inflammaging and is therapeutically available. A successful outcome of this study will provide a direct avenue toward translation in pro-regenerative and anti-aging therapies.

描述（由申请人提供）：低级慢性炎症是衰老过程的标志。 NTI炎症（M2）。在鼠类病模型中的再生。为了检验这一假设，申请人在苍蝇和小鼠中进行了预知：（i）果蝇中MANF对与衰老相关的表型的影响，以评估MANF在小鼠中与年龄相关的炎症中的作用（iii）测试MANF作为与年龄相关的疾病的潜在疗法。促进促进和抗抗抗原的terapies。